ubiquitin-conjugating enzyme E2 D3; ubiquitin carrier protein D3; ubiquitin-conjugating enzyme E2(17)KB 3; ubiquitin-conjugating enzyme E2-17 kD 3; ubiquitin-protein ligase D3 (UBE2D3, UBC5C, UBCH5C)

Function

• accepts ubiquitin from the E1 complex & catalyzes its covalent attachment to other proteins
• in vitro catalyzes Lys-11-, as well as Lys-48-linked polyubiquitination
• cooperates with the E2 CDC34 & the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation
• acts as an initiator E2, priming the phosphorylated NFKBIA target at positions Lys-21 &/or Lys-22 with a monoubiquitin
• ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA- linked ubiquitin
• also acts as an initiator E2, in conjunction with RNF8, for priming of PCNA
• monoubiquitination of PCNA, & its subsequent polyubiquitination, are events in the DNA damage tolerance pathway that is activated after DNA damage caused by UV or chemical agents during S-phase
• associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair
• targets DAPK3 for ubiquitination which influences PML body formation in the nucleus
• in conjunction with the MDM2 & TOPORS E3 ligases, facilitates ubiquitination of p53/TP53
• facilitates NRDP1-mediated ubiquitination & degradation of ERBB3 & of BRUCE which triggers apoptosis
• in conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization & transport on endosomes
• in conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction (putative)
• protein modification; protein ubiquitination
• interacts with SCF E3 ubiquitin ligase complex;
  • when Cullin is neddylated, the interaction between the E2 & the SCF complex is strengthened
• interacts with DAPK3
• interacts with BRCA1; DNA damage checkpoint promotes the association with BRCA1 after ionizing radiation
• interacts non-covalently with ubiquitin

Structure

• belongs to the ubiquitin-conjugating enzyme family

Compartment

• cell membrane; peripheral membrane, endosome membrane

Alternative splicing

named isoforms=3

More general terms

• ubiquitin-conjugating protein E2 (ubiquitin carrier protein)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7323
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7323
• OMIM: https://mirror.omim.org/entry/602963
• UniProt: http://www.uniprot.org/uniprot/P61077.html